Children’s internalizing behavior development is heterogeneously associated with the pace of epigenetic aging

Juan Carlos Caro, Cyrielle Holuka, Giorgia Menta, Jonathan Turner, Claus Vögele, Conchita D'Ambrosio

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Internalizing behaviors are an indicator of children’s psychological and emotional development, predicting future mental disorders. Recent studies have identified associations between DNA methylation (DNAm) and internalizing behaviors. This prospective study aimed at exploring the associations between pace of biological aging and the developmental trajectories of internalizing behaviors.

Participants were children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort (N = 974). Measures of DNA methylation were collected at birth, age 7 and ages 15–17. The pace of aging was estimated using the DunedinPoAm algorithm (PoAm). Internalizing behaviors reported by caregivers between ages 4 and 16 using the Strengths and Difficulties Questionnaire. To explore heterogeneity in the association between PoAm and internalizing behaviors we use Poisson quantile regression in cross-section heterogeneity and longitudinal latent class analysis over the childhood and adolescence.

Internalizing behavior trajectories were identified: low-risk, childhood limited, late onset and early onset (persistent). Accelerated aging at birth was negatively associated with internalizing behaviors in early childhood but positively correlated during adolescence. Higher PoAm at birth increased chance of low-risk profile, while decreasing likelihood of childhood limited trajectory. PoAm at age 15 was negatively associated with childhood limited profile and positively linked to late onset trajectories. Associations were larger at higher values of internalizing symptoms.

The heterogeneity in the association between biological age acceleration and internalizing behaviors suggests a complex dynamic relationship, particularly in children with high or increased risk of adverse mental health outcomes.
Original languageEnglish
Article number108463
JournalBiological Psychology
Early online date24 Nov 2022
Publication statusPublished - Jan 2023

Bibliographical note

We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (Grant ref: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and will serve as guarantors for the contents of this paper. Financial support from the Fonds National de la Recherche Luxembourg (Grant C19/SC/13650569/ALAC) is gratefully acknowledged.


  • DNA
  • Acelerated aging
  • internalizing behviors
  • children

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